SLAM family receptors control pro-survival effectors in germinal center B cells to promote humoral immunity

Expression of the signaling lymphocytic activation molecule (SLAM)–associated protein (SAP) is critical for the germinal center (GC) reaction and T cell–dependent antibody production. However, when SAP is expressed normally, the role of the associated SLAM family receptors (SFRs) in these processes is nebulous. Herein, we established that in the presence of SAP, SFRs suppressed the expansion of the GC reaction but facilitated the generation of antigen-specific B cells and antibodies. SFRs favored the generation of antigen-reactive B cells and antibodies by boosting expression of pro-survival effectors, such as the B cell antigen receptor (BCR) and Bcl-2, in activated GC B cells. The effects of SFRs on the GC reaction and T cell–dependent antibody production necessitated expression of multiple SFRs, both in T cells and in B cells. Hence, while in the presence of SAP, SFRs inhibit the GC reaction, they are critical for the induction of T cell–mediated humoral immunity by enhancing expression of pro-survival effectors in GC B cells.     

Perioperative safety and short-term efficacy of functional minimally invasive esophagectomy

BackgroundStandard minimally invasive McKeown three-field esophagectomy (SMIE) results in high perioperative risk and poor postoperative quality of life owing to considerable surgical damage and numerous postoperative complications. We created a modified procedure, functional minimally invasive esophagectomy (FMIE), which preserves the azygos arch, bronchial artery, pulmonary branch of the vagus nerve, and the mediastinal pleura. Our aim was to evaluate the efficacy and safety of FMIE and to determine whether it has limited invasiveness.MethodsBetween 2018 and 2020, FMIE was performed for 48 patients who were compared with 76 SMIE cases; 44 paired cases were matched using propensity score matching.ResultsOperation time, extubation time, and postoperative hospital stay were significantly lower in the FMIE group. FMIE was also associated with fewer pulmonary infections. Postoperative drainage volume on postoperative day (POD) 1 and POD 2, and white blood cell counts on POD 2 and POD 4 were also significantly lower in the FMIE group. There was no statistically significant difference in the number of dissected lymph nodes, short-term recurrence, metastasis rates, or survival rate between the two groups.ConclusionsFMIE is a less invasive procedure and may be a suitable alternative for lower and early middle esophageal carcinoma.     

Association between serum visfatin levels and psoriasis and their correlation with disease severity: a meta-analysis

ObjectiveTo determine the association between serum visfatin levels and psoriasis and to evaluate the correlation between serum visfatin levels and the severity of psoriasis.MethodsThe electronic databases PubMed®, Embase® and the Cochrane Library were searched for articles published from inception to 1 May 2020. Data were extracted and then standard mean differences (SMDs) and 95% confidence intervals (CIs) were calculated for pooled estimates.ResultsA total of 11 studies met the inclusion criteria and were included (448 patients diagnosed with psoriasis and 377 controls). This meta-analysis demonstrated that patients with psoriasis had significantly higher levels of visfatin than the controls (SMD = 0.90, 95% CI 0.52, 1.28). Subgroup analyses showed that differences in serum visfatin levels between the patient group and the control group were associated with ethnicity, Psoriasis Area and Severity Index (PASI) and body mass index. Additionally, a meta-analysis of correlations showed that visfatin levels in patients with psoriasis were positively correlated with PASI (r = 0.51, 95% CI 0.14, 0.75).ConclusionsThis meta-analysis showed that serum visfatin levels in patients with psoriasis were significantly higher than those in the controls and a positive correlation between serum visfatin levels and psoriasis severity was observed.     

2015－2019年中国居民心脑血管事件报告数据质量分析

  目的  分析2015 — 2019年中国居民心脑血管事件报告数据质量。  方法  选取河北、江苏、浙江、湖北和四川5个省10个国家心脑血管事件报告监测点,抽取2015 — 2019年其辖区内1家二级及以上医疗机构报告的“脑卒中急性事件报告卡”和“急性心肌梗死事件报告卡”（来源于中国疾病预防控制中心“全民健康保障信息化疾病预防控制信息系统”）若干份,利用中国疾病预防控制中心慢性非传染性疾病预防控制中心开发的“心脑血管事件质量研究信息系统”,由相关人员采集相应的临床资料,复核判定报告卡填写的完整性和准确性。  结果  查找并复核急性脑卒中事件报告卡2 184份核心变量报告完整率为100.00%,核心变量报告准确率为79.21%～95.15%,经复核有2 062份是脑卒中急性发作事件,阳性预测值为94.41%（93.07%～96.14%）。 2015 — 2019年脑卒中核心变量报告准确性呈现增高趋势（P<0.001）。 查找并复核急性心肌梗死报告卡699份,核心变量报告完整率为100.00%,核心变量报告准确率为75.10%～95.42%,经复核有668份为急性心肌梗死事件,阳性预测值为95.57%（92.86%～97.45%）。 2015 — 2019年急性心肌梗死报告卡诊断依据完整性和核心变量准确性呈现增长趋势（均P<0.001）。  结论  2015 — 2019年心脑血管事件报告卡完整性较高,报告准确性逐渐提升,仍然存在着一定比例的错报,需要进一步加强报告规范性。     

Interleukin-17A promotes rheumatoid arthritis synoviocytes migration and invasion under hypoxia by increasing MMP2 and MMP9 expression through NF-κB/HIF-1α pathway

Both hypoxia and interleukin-17A (IL-17A) promote the migration and invasion of fibroblast-like synoviocytes (FLSs), which are critical for the pathogenesis of rheumatoid arthritis (RA). However, the biochemical pathways regulating IL-17A combined with hypoxia are not well defined. In this study, we found that co-stimulating RA-FLSs with IL-17A and hypoxia did not appear to promote the epithelial–mesenchymal transition (EMT), but did increase cell motility. We further showed that a proinvasive effect of IL-17A on FLSs under hypoxia might be through upregulation of matrix metalloproteinase 2 (MMP2) and MMP9. Moreover, IL-17A-induced expression of MMP2 and MMP9 under hypoxia was accompanied by increased activation of nuclear factor-κB (NF-κB)/hypoxia-inducible factor-1α (HIF-1α). Knockdown or inhibition of HIF-1α and NF-κB by small interfering RNA or specific small molecule inhibitors blocked IL-17A-mediated and hypoxia-mediated MMP2 and MMP9 expression, cell migration, and invasion. In addition, the inhibition of NF-κB led to a marked decrease in the expression of HIF-1α, which indicated that IL-17A activated HIF-1α via the NF-κB pathway in hypoxia. Taken together, our observations suggest a synergetic effect of IL-17A and hypoxia that might contribute to the migration and invasion of RA-FLSs by upregulating the expression of MMP2 and MMP9 by activation of the NF-κB/HIF-1α pathway.     

Transmissible gastroenteritis virus infection induces cell cycle arrest at S and G2/M phases via p53-dependent pathway

p53 signaling pathway plays an important role in the regulation of cell cycle. Our previous studies have demonstrated that TGEV infection induces the activation of p53 signaling pathway. In this study we investigated the effects of TGEV infection on the cell cycle of host cells and the roles of p53 activation in this process. The results showed that TGEV infection induced cell cycle arrest at S and G2/M phases in both asynchronous and synchronized PK-15 and ST cells, while UV-inactivated TGEV lost the ability of induction of cell cycle arrest. TGEV infection promoted p21 accumulation, down-regulated cell cycle-regulatory proteins cyclins B1, cdc2, cdk2 and PCNA. Further studies showed that inhibition of p53 signaling could attenuate the TGEV-induced S- and G2/M-phase arrest by reversing the expression of p21 and corresponding cyclin/cdk. In addition, TGEV infection of the cells synchronized in various stages of cell cycle showed that viral genomic RNA and subgenomic RNA, and virus titer were higher in the cells released from S-phase- or G2/M phase-synchronized cells than that in the cells released from the G0/G1 phase-synchronized or asynchronous cells after 18 h p.i. Taken together, our data suggested that TGEV infection induced S and G2/M phase arrest in host cells, which might provide a favorable condition for viral replication.     

Using next-generation sequencing as a genetic diagnostic tool in rare autosomal recessive neurologic Mendelian disorders

Next-generation sequencing was used to investigate 9 rare Chinese pedigrees with rare autosomal recessive neurologic Mendelian disorders. Five probands with ataxia-telangectasia and 1 proband with chorea-acanthocytosis were analyzed by targeted gene sequencing. Whole-exome sequencing was used to investigate 3 affected individuals with Joubert syndrome, nemaline myopathy, or spastic ataxia Charlevoix-Saguenay type. A list of known and novel candidate variants was identified for each causative gene. All variants were genetically verified by Sanger sequencing or quantitative polymerase chain reaction with the strategy of disease segregation in related pedigrees and healthy controls. The advantages of using next-generation sequencing to diagnose rare autosomal recessive neurologic Mendelian disorders characterized by genetic and phenotypic heterogeneity are demonstrated. A genetic diagnostic strategy combining the use of targeted gene sequencing and whole-exome sequencing with the aid of next-generation sequencing platforms has shown great promise for improving the diagnosis of neurologic Mendelian disorders.     

Effects of the glucose-lowering rate on cTnI and hs-CRP serum levels in type 2 diabetics

Objectives

The current objective is to evaluate the effect of intensive glycemic control on serum levels of both Cardiac Troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP) in subjects with type 2 diabetes. Hence, we are trying to find a reasonable glucose-lowering rate associated with type 2 diabetics with and without coronary heart disease.

Methods

A total of 132 type 2 diabetes mellitus without coronary heart disease (T2DM) cases and 135 type 2 diabetes mellitus with coronary heart disease (T2DM+CHD) cases received intensive glycemic control. Serum cTnI and hs-CRP levels were tested before and after intensive glycemic control.

Results

There was no significant difference in the changing amplitude of cTnI and hs-CRP serum levels variation between four glucose-lowering rates in T2DM group (P > 0.05), while this difference was observed in T2DM+CHD group(P < 0.05). During the follow-up, cTnI and hs-CRP serum levels were lower than those before glycemic control in both T2DM and T2DM+CHD groups (P < 0.05).

Conclusions

The glucose-lowering rate in T2DM+CHD group should be no more than 4 mmol L⁻¹ d⁻¹ and the appropriate glucose-lowering rate in T2DM group is no more than 6 mmol L⁻¹ d⁻¹. Serum levels of cTnI and hs-CRP will be increased if the glucose-lowering rate is over this range, which means that cardiovascular endpoints might be induced.     

High-Resolution Melting Curve Analysis for Rapid Detection of Rifampin Resistance in Mycobacterium tuberculosis: a Meta-Analysis

A rapid, simple, accurate, and affordable method for the detection of drug-resistant tuberculosis is very critical for the selection of antimicrobial therapy and management of patient treatment. High-resolution melting curve analysis has been used for the detection of rifampin resistance in Mycobacterium tuberculosis and has shown promise. We did a systematic review and meta-analysis of published studies to evaluate the accuracy of high-resolution melting curve analysis for the detection of rifampin resistance in clinical M. tuberculosis isolates. We searched the PubMed, BIOSIS Previews, and Web of Science databases to identify studies and included them according to predetermined criteria. We used the DerSimonian-Laird random-effects model to calculate pooled measures and applied Moses'' constant for linear models to fit the summary receiver operating characteristic curve. According to the selection criteria, most of the identified studies were excluded, and only seven studies were included in the final analysis. The overall sensitivity of the high-resolution melting curve analysis was 94% (95% confidence interval [CI], 92% to 96%), and the overall specificity was very high at 99% (95% CI, 98% to 100%). The values for the pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 63.39 (95% CI, 30.21 to 133.00), 0.06 (95% CI, 0.04 to 0.09), and 892.70 (95% CI, 385.50 to 2,067.24), respectively. There was no significant heterogeneity across all included studies for the measurements we evaluated. The summary receiver operating characteristic curve for the same data shows an area of 0.99 and a Q* value of 0.97. High-resolution melting curve analysis has high sensitivity and specificity for the detection of rifampin resistance in clinical M. tuberculosis isolates. This method might be a good alternative to conventional drug susceptibility tests in clinical practice.     

Ischemia preconditioning is neuroprotective in a rat cerebral ischemic injury model through autophagy activation and apoptosis inhibition

Sublethal ischemic preconditioning (IPC) is a powerful inducer of ischemic brain tolerance. However, its underlying mechanisms are still not well understood. In this study, we chose four different IPC paradigms, namely 5 min (5 min duration), 5×5 min (5 min duration, 2 episodes, 15-min interval), 5×5×5 min (5 min duration, 3 episodes, 15-min intervals), and 15 min (15 min duration), and demonstrated that three episodes of 5 min IPC activated autophagy to the greatest extent 24 h after IPC, as evidenced by Beclin expression and LC3-I/II conversion. Autophagic activation was mediated by the tuberous sclerosis type 1 (TSC1)-mTor signal pathway as IPC increased TSC1 but decreased mTor phosphorylation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and hematoxylin and eosin staining confirmed that IPC protected against cerebral ischemic/reperfusion (I/R) injury. Critically, 3-methyladenine, an inhibitor of autophagy, abolished the neuroprotection of IPC and, by contrast, rapamycin, an autophagy inducer, potentiated it. Cleaved caspase-3 expression, neurological scores, and infarct volume in different groups further confirmed the protection of IPC against I/R injury. Taken together, our data indicate that autophagy activation might underlie the protection of IPC against ischemic injury by inhibiting apoptosis.